CN101646416A - Composition for external application to skin - Google Patents

Abstract

Disclosed is a humectant or composition for external application to skin, which contains one or more compounds selected from the group consisting of lysyl-ss-alanine represented by the general formula(1) below and salts thereof.

Description

Composition for external application

Technical field

The present invention relates to composition for external application.

In more detail, relate to excellent in safety, usability excellence, permeability excellence, directly act on horny layer and increase water quantities in the horny layer, continue the wetting agent of moistening effect excellence, and relate to and directly act on horny layer and to increase moisture, excellent in safety, excellent in stability, usability in the horny layer excellent and have moistening effect and prevent, improve the composition for external application of wrinkle effect.

Background technology

Wear out and in the internal organs of whole body, carrying out, wherein, make many person in middle and old age persons in the society, especially women's worry at aging produced simultaneously wrinkle and microgroove for the skin that can be discovered by naked eyes, the face that especially arouses attention especially easily.All the time, to improve the demand that wrinkle applies some make up strong to such, adapts therewith, carried out various trials up to now, but unclear for the mechanism major part that relates to aging and wrinkle, thereby do not occur the gratifying invention of effect as yet.On the other hand, wherein, increase and maintenance can keep the skin softness, keep elasticity and protect corium as the outermost cuticular moisture of epidermis, therefore, can expect to realize some fixed target.

Wherein, all the time, in order to improve moistening effect, and improve usability, safety, purpose such as anticorrosion cooperates wetting agent in composition for external application.For example can enumerate, glycerol, 1,3 butylene glycol, xylitol, Sorbitol, erithritol, maltose alcohol, Polyethylene Glycol, propylene glycol, diglycerol (EO) be polyol, polyethers such as addition product (PO).Though these wetting agents have moistening effect, prevention, improve the effect of wrinkle and insufficient, and have usability problem such as be clamminess, produce problem such as abnormal smells from the patient owing to oxidation.

In addition, hyaluronic acid, mucoitin sulfuric acid, chondroitin sulfate, soluble collagen, go to hold peptide collagen macromolecular compounds such as (atelocollagen) also to be used as wetting agent to use.Though these macromolecular compounds are than moistening effect height such as polyol classes, to preventing, improving wrinkle, moistening effect is still insufficient.In addition, its effect also is preserving moisture of skin surrounding, and macromolecular compound is not directly to play a role in skin to the poor permeability of skin.In addition, need neutralize when exist cooperating, the such problem of operation such as dissolving, cause tight sense by the tunicle sense, than the problem of such usability that are clamminess more such as polyol class.

As the low molecular compound except that the polyol class, sodium lactate, bile salts, pyrrolidone carboxylic acid salt, amino acids also are widely used as wetting agent.Because they are low molecular compounds, thus can expect to be penetrated in the horny layer, by they performance function itself, but the moistening effect of these chemical compounds itself is not high.And, because these chemical compounds are crystallinity height, low to the dissolubility of the solvent beyond dewatering all, thereby in being coupled to composition for external application the time, exist and to evapotranspire and separate out along with moisture after smearing, the continuous capability of moisture retention is poor, is suppressed such problem to cuticular infiltration simultaneously.In addition, particularly amino acids is understood sensigenous more stimulates, for example, glycine, Beta-alanine, GABA (γ-An Jidingsuan) etc., particularly the user of sensitive skin can be felt skin irritation when smearing, thereby use level is restricted.In addition, also produce the problem of abnormal smells from the patient, for example low molecule basic amino acid such as lysine can produce amine sample gas flavor, thereby in the composition for external application that is applied in probably near the face of nose etc., use level still is restricted.

The present inventor In view of the foregoing, for having high moistening effect, the persistence of preserving moisture excellence, problems such as numbness stimulation and abnormal smells from the patient, safe, the permeability excellence, directly act on horny layer and increase water quantities in the horny layer, the material of the excellent in stability of the composition for external application that fits in is furtherd investigate, found that, lysyl-Beta-alanine of the present invention and salt thereof are the excellent moistening effects of performance, the persistence of preserving moisture excellence, the permeability height, directly act on horny layer and increase water quantities in the horny layer, the problem that numbness stimulates when smearing, the material of excellent in safety, the problem that does not also have abnormal smells from the patient, and modulate composition for external application easily, the excellent in stability of synthetic composition for external application, the usability excellence, thus the present invention finished.

Patent documentation 1: Japanese patent laid-open publication gazette is put down into 8-11746 number

Summary of the invention

The purpose of this invention is to provide that numbness stimulates and problem, excellent in safety, usability excellence, the permeability excellence of abnormal smells from the patient, directly act on horny layer and increase water quantities in the horny layer, continue the wetting agent of moistening effect excellence, and provide directly act on horny layer and increase water quantities in the horny layer, continue the moistening effect excellence, numbness stimulates and abnormal smells from the patient problem, safety and excellent in stability, usability is excellent and have moistening effect and prevent, improve the composition for external application of wrinkle effect.

That is, the invention provides a kind of wetting agent, contain the chemical compound more than a kind or 2 kinds that is selected from lysyl-Beta-alanine shown in the following general formula (1) and the salt thereof.

In addition, the present invention also provides a kind of and directly acts on horny layer and increase that the water quantities in the horny layer, the persistence of preserving moisture excellence, numbness stimulate and abnormal smells from the patient problem, safety and excellent in stability, usability is excellent and have moistening effect and prevent, improve the composition for external application of wrinkle effect, it is characterized in that, contain the chemical compound that is selected from lysyl-Beta-alanine shown in the general formula (1) and their salt.

According to the present invention, can provide and have excellent moistening effect, the persistence excellence of moistening effect, numbness stimulates and the abnormal smells from the patient problem, excellent in safety, the usability excellence, the percutaneous permeability excellence, directly act on horny layer and increase water quantities in the horny layer, have the wetting agent of lasting moistening effect, and the percutaneous permeability excellence is provided, directly act on keratodermatitis and increase water quantities in the horny layer, the persistence of preserving moisture excellence, excellent in safety, excellent in stability, numbness stimulates and the abnormal smells from the patient problem, the usability excellence, and have moistening effect and prevent, improve the composition for external application of wrinkle effect.

The specific embodiment

Wetting agent of the present invention contains the lysyl-Beta-alanine shown in a kind or the multiple above-mentioned general formula (1) or its salt as the active component with moistening effect.In addition, composition for external application of the present invention contains lysyl-Beta-alanine or its salt shown in a kind or the multiple above-mentioned general formula (1).

Lysyl-Beta-alanine shown in the employed general formula (1) among the present invention is the known compound of using with N-(2,6-diaminourea caproyl)-chemical names such as 2-alanine.This lysyl-Beta-alanine is the dipeptides that is made of lysine and Beta-alanine, for lysine, can be L body, D body, DL body, thereby this lysyl-Beta-alanine can make L-lysyl-Beta-alanine, D-lysyl-Beta-alanine or D, L-lysyl-Beta-alanine.In the present invention, can be any form, both can be the DL body, can its composition be arbitrarily also.

The application of lysyl-Beta-alanine in the nerve centre medicine is known, but of the present invention to have moistening effect be novel, and using in composition for external application also is novel (patent documentation 1).

Employed lysyl-Beta-alanine can be easily synthetic by known method among the present invention, in addition, also can extract use from natural goods etc. or obtain by methods such as enzyme process.

The salt of the lysyl-Beta-alanine shown in the mutual-through type (1) is restriction especially not; for example can enumerate; hydrochlorate; sulfate; phosphate; hydrobromate; alkyl sulfate such as Methylsulfate and tosilate; acetate; lactate; maleate; fumarate; oxalates; succinate; tartrate; hydrochlorates such as citrate; the Radix Betae alkali salt; glycinate; alanine salt; serine salt; taurate; glutamate, Glu; the salt of aspartate etc. and amino acids; sodium salt; potassium salt; magnesium salt; calcium salt; ammonium salt; triethanolamine salt; diethanolamine salt etc., but the present invention is not limited to this.In addition, lysyl-Beta-alanine can be arbitrarily with the ratio of the salifiable gegenion of structure, can also make up with a plurality of gegenions.

In the present invention, the lysyl-Beta-alanine shown in the general formula (1) or the use level of its salt are 0.001～20.0 quality % in wetting agent or composition for external application total amount, are preferably 0.1～10.0 quality %.Think if be lower than 0.001 quality % then lack effect, even and cooperate and surpass 20.0 quality % and can not expect to increase effect.

Compositions involved in the present invention can be according to the conventional method manufacturing, in addition, as the composition that constitutes compositions, both can use separately the lysyl-Beta-alanine shown in the general formula (1) or its salt a kind or 2 kinds with on modulate, also can suitably cooperate as required usually and comprise the cosmetics of quasi drug, the composition that uses in the skin preparations for extenal use such as medicine etc., for example oil content, surfactant, powder, colorant, water, alcohols, thickening agent, chelating agen, type siloxane, antioxidant, UV absorbent, wetting agent, spice, various active ingredient, antiseptic, pH adjusts agent, nertralizer etc.

In any gradation composition of above-mentioned suitable cooperation, as oil content, can enumerate straight chain alcohols such as lauryl alcohol, spermol, octadecanol, tetradecanol, oleyl alcohol, higher alcohols such as branched-chain alcoho such as single batiolum, lanolin alcohol, cholesterol, plant sterol, isooctadecane alcohol; Senior fatty acids such as lauric acid, tetradecanoic acid, Palmic acid, stearic acid; Hard paraffin, Cera Flava, hardened castor oil, Brazil wax, WB wax waxes such as (バ リ コ ワ Star Network ス); Animal and plant fats such as Adeps Bovis seu Bubali, Adeps Sus domestica, Adeps Caprae seu ovis, squalane, Oleum Cocois, Petiolus Trachycarpi oil, palm-kernel oil, soybean oil, olive oil, Oleum Gossypii semen, Jojoba oil, Oleum Ricini, lanoline; Mineral oil such as liquid paraffin, vaseline; Trimethyl propane three isostearates, isopropyl myristate, three (2 ethyl hexanoic acid) glyceride, four (2 ethyl hexanoic acid) pentaerythritol ester, silicone oil, polyoxyethylene (below, also be designated as POE) synthetic wet goods such as polyoxypropylene (below, also be designated as POP) tetramethylolmethane ether.

As surfactant, can enumerate soap substrate, sodium laurate, fatty acid soaps such as sodium palmitate, sodium lauryl sulphate, senior alkyl sulfate salt such as lauryl sulphate acid potassium, the POE dodecyltriethanolamine sulfate, alkyl ether sulphate salts such as POE sodium lauryl sulphate, N-acyl group sarcosine such as sodium lauroyl sarcosine, N-tetradecanoyl-N methyl taurine sodium, senior fatty acid amide sulfonic acid such as coco-nut oil fatty acid methylamino ethyl sulfonic acid sodium, phosphate ester salts such as POE octadecyl ether phosphoric acid, single lauroyl single ethanol amide POE sodium sulfosuccinate, sulfosuccinates such as dodecyl polypropylene glycol sodium sulfosuccinate, linear dodecylbenzene sodium sulfonate, alkylbenzenesulfonates such as linear DBSA triethanolamine, N-stearoyl-glutamic acid disodium, N-acyl glutamates such as N-stearoyl-glutamic acid list sodium, senior fatty acid ester sulfuric acids such as sclerosis coco-nut oil fatty acid glyceride sodium sulfate, Turkey red wet goods sulfated oil, the POE alkyl ether carboxylic acid, POE alkyl allyl ether carboxylate, the higher fatty acids sulfonated ester, the secondary alcohol sulfuric acid, higher fatty acids alkylolamides sulfuric acid, lauroyl single ethanol amide sodium succinate, aniones such as casein sidium are surfactant;

Alkyl trimethyl ammonium salt such as octadecyl trimethyl ammonium chloride, Dodecyl trimethyl ammonium chloride, dialkyl dimethyl ammonium salts such as two (octadecyl) alkyl dimethyl ammonium chloride salt, Fixanols such as hexadecylpyridinium chloride, alkyl quaternary ammonium salts, alkyl dimethyl benzyl ammonium salt, alkyl isoquinolinium salt, dialkyl group alkylbenzyldimethylasaltsum saltsum, POE alkylamine, alkylamine salt, the polyamine derivative of fatty acid, the amylalcohol derivative of fatty acid, cationes such as benzalkonium chloride are surfactant; 2-cocoyl-2-hydroxide imidazoles-imidazolines such as 1-carboxyl ethyoxyl disodium salt are amphoteric surfactant, and betanins such as amide betaine, sulfobetaines are amphoteric surfactantes such as surfactant; Dehydrating sorbitol monooleate, anhydrosorbitol list isostearate, sorbitan monolaurate, sorbitan-monopalmityl ester, sorbitan fatty ester classes such as anhydrosorbitol trioleate, single cottonseed oil fatty acid glyceride, glyceryl monostearate, the sesquialter olein, glycerol polyglyceryl fatty acid ester classes such as glyceryl monostearate malate, methyl glycol fatty acid ester classes such as propylene glycolmonostearate, the hardened castor oil derivant, the glycerol alkyl ether, lipophile non-ionic surface active agents such as POE-methyl polysiloxane copolymer; The POE dehydrating sorbitol monooleate, POE sorbitan fatty ester classes such as POE anhydrosorbitol monostearate, POE is sorbityl monododecanoate, the POE sorbitol monooleate, POE Sorbitol fatty acid esters such as POE Sorbitol monostearate, the POE glyceryl monooleate, POE glycerine fatty acid esters such as POE glycerol distearate, the POE monoleate, the POE distearate, POE fatty acid esters such as the single dioleate of POE, the POE lauryl ether, the POE oleyl ether, POE alkyl ethers such as POE cholestane alcohol ester, the POE octyl phenyl ether, POE alkyl phenyl ethers such as POE nonylplenyl ether, polyether-type classes such as Pluronic, the POE-POP monobutyl ether, the POE-POP cetyl ether, POE-POP alkyl ethers such as POE-POP glycerin ether, the POE Oleum Ricini, the POE hardened castor oil, POE hardened castor oil list isostearate, POE Oleum Ricini hardened castor oil derivants such as POE hardened castor oil maleic acid, POE Apis cerana Fabricius-lanolin derivatives such as POE Sorbitol Apis cerana Fabricius, cocoanut fatty acid diethanolamide, alkanolamides such as fatty acid isopropanol amide, the POE methyl glycol fatty acid ester, the POE fatty acid amide, the POE alkylamine, sucrose fatty acid ester, hydrophilic non-ionic surfactant such as alkyl ethoxy dimethyl oxidation amine etc.

As alcohols, can enumerate lower alcohols such as ethanol, propanol, isopropyl alcohol etc.

As thickening agent, can enumerate Radix Acaciae senegalis, Tragacanth, galactan, algaroba glue, guar gum, carrageenan, pectin, agar, starch (corn, Semen Tritici aestivi, Rhizoma Solani tuber osi, rice) department of botany's macromolecule such as, glucosan, department of microbiology macromolecules such as amylopectin, carboxymethyl starch, starch such as methyl hydroxypropyl starch are macromolecule, collagen, casein, animals such as gelatin are macromolecule, methylcellulose, nitrocellulose, ethyl cellulose, hydroxyethyl-cellulose, cellulose sodium sulfate, hydroxypropyl cellulose, carboxymethyl cellulose, cellulose-based macromolecule such as crystalline cellulose, sodium alginate, alginic acid such as propylene glycol alginate are macromolecule, the polyvinyl methyl ether, ethylene such as CVP Carbopol ETD2050 are macromolecule, POE is a macromolecule, POE-POP copolymerization system macromolecule, sodium polyacrylate, acrylic acid series macromolecules such as polyacrylamide, polymine, cationic polymer, bentonite, Magnesiumaluminumsilicate, LAPONITE, Strese Hofmann's hectorite., silicic acid anhydrides etc. are inorganic to be water soluble polymers such as water soluble polymer etc.

As chelating agen, can enumerate citramalic acid (Citramalic acid), agaric acid (agaric acid), glyceric acid, shikimic acid, hinokitiol, gallic acid, tannic acid, caffeic acid, ethylenediaminetetraacetic acid, glycol diamine tetraacethyl, diethylene-triamine pentaacetic acid, phytic acid, polyphosphoric acid, Metaphosphoric acid and their analog and their alkali metal salt and carboxylate etc.

As UV absorbent, can enumerate benzoic acid such as para-amino benzoic acid is UV absorbent; Ortho-aminobenzoic acids such as methyl 2-aminobenzoate are UV absorbent; Salicylic acid such as ethylhexyl salicylate are UV absorbent; Cinnamic acid such as p-methoxycinnamic acid isopropyl ester, p-methoxycinnamic acid monooctyl ester are UV absorbent etc.

As wetting agent, can enumerate Polyethylene Glycol, propylene glycol, dipropylene glycol, 1,3 butylene glycol, glycerol, diglycerol, xylitol, maltose alcohol, maltose, D-mannitol, glucose, fructose, sodium chondroitin sulfate, hyaluronate sodium, sodium lactate, glycosamine, cyclodextrin etc.

As active ingredient, can cooperate vitaminss such as vitamin A oil, retinol, retinyl palmitate, pyridoxine hydrochloride, benzyl nicotinate, nicotiamide, nicotinic acid dl-alpha-tocopherol esters, magnesium ascorbyl phosphate, vitamin D2, dl-alpha-tocopherol, pantothenic acid, biotin; Antiinflammatory such as azulenes, glycyrrhizin; Whitening agents such as arbutin, 4-methoxyl group potassium salicylate, 2-O-ethyl ascorbic acid, ascorbic acid glucoside; Hormoness such as estradiol; Astringent such as zinc oxide, tannic acid; Fresheners such as L-menthol, Camphora; And lysozyme chloride, pyridoxine hydrochloride, sulfur etc.And then can cooperate the various extracts that show multiple drug effect.Can enumerate Herba Houttuyniae extract, Cortex Phellodendri extract, Radix Glycyrrhizae extract, Radix Paeoniae Alba extract, Cortex Moutan extract, Fructus Luffae extract, Herba Saxifragae extract, eucalyptus extracts, Flos Caryophylli extract, Aesculus chinensis Bunge (marronnier) extract, Centaurea cyanus extract, Sargassum extract, Thymi Serpylli Herba extract etc.

As antiseptic, can enumerate parabenses such as methyl parahydroxybenzoate, ethylparaben, butyl p-hydroxybenzoate, benzoic acid, salicylic acid, sorbic acid, parachlorometacresol, hexachlorophene, benzalkonium chloride, Chlorhexidine hydrochloride, Amolden MCM 400, sensitization element, phenyl phenol, Methylisothiazolinone etc.

As nertralizer, can enumerate 2-amino-2-methyl-1-propanol, 2-amino-2-methyl-1, ammediol, potassium hydroxide, potassium hydroxide, triethanolamine, sodium carbonate etc.

Adjust agent as pH, can enumerate lactic acid, citric acid, glycolic, succinic acid, tartaric acid, malic acid, sodium bicarbonate, ammonium bicarbonate etc.

As antioxidant, can enumerate ascorbic acid, alpha-tocopherol, carotenoid etc.

Mentioned component is an illustration, is not limited to these compositions.These compositions can carry out appropriate combination and cooperate according to the prescription according to required mode in addition.

Not restriction especially of dosage form to wetting agent of the present invention and composition for external application, for example, can adopt dosage form arbitrarily such as solution system, solubilizing systems, emulsion type, powder disperse system, water-oily two series of strata, water-oil-powder three series of strata, ointment, gel, aerosol.In addition, to occupation mode also not restriction especially, for example, can adopt any-modes such as astringent, emulsion, emulsifiable paste, elite, jelly (jelly), gel, ointment, facial film (pack), facial film (mask), foundation cream.

Wetting agent of the present invention and composition for external application can be by being applied to skin, thereby are being used to realize skin moisture-keeping, use in the beauty method that prevention forms wrinkle and/or makes established wrinkle alleviate, disappear.Usage, also not restriction especially of consumption to wetting agent of the present invention and composition for external application in this beauty method, can suitably determine according to the wrinkle state of the skin of dosage form, processing, be typically, can with every day for several times, for example 1 time～5 times, every square centimeter of 0.1ml～1ml for example in right amount,, directly wipe on skin, perhaps after in an amount of wetting agent of the present invention and the composition for external application immersion gauze etc., be fitted on the skin.

Embodiment

Illustrate in greater detail the present invention below by enumerating embodiment.The invention is not restricted to this.

[Production Example of L-lysyl-Beta-alanine]

With 2.2g N, N '-benzyloxy carbonyl-L-lysine is dissolved in the 40mL dichloromethane, at room temperature add 1.9g Beta-alanine benzyl ester toluene fulfonate, 1.5mL triethylamine, 1.0g 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride, 0.8g I-hydroxybenzotriazole, stirred 3 hours.With 100mL dichloromethane dilution, reuse 50mL purifies waste water, the 2M hydrochloric acid of 50mL, the water washing of 50mL saturated common salt, carries out drying with anhydrous magnesium sulfate then, concentrates after filtering.In the residue that obtains, add 200mL methanol, add 0.5g palladium carbon (5%, humidity 50%) again, under hydrogen atmosphere, at room temperature stirred 2 hours, filtering and concentrating and obtain goal object 1.1g (96%).

[test of keratodermatitis moistening effect]

Mensuration has been smeared the hairless mouse (HR-1: the variation of the cuticlar water component at the back wild laboratory animal of star) of medicament.Test is carried out under the condition of n=5, and (skin conductor ASA-MX) measures the cuticlar water component to use skin conductor.After measuring the cuticlar water component, smear embodiment 1, comparative example 1～comparative example 5,1 days 1 time that the following demonstration of 100 μ l forms respectively at the mensuration position of mouse back.After smearing continuously 2 days, measuring the cuticlar water component, after further smearing continuously 2 days, measuring the cuticlar water component from the 5th day on-test from the 3rd day on-test.

Embodiment 1

L-lysyl-Beta-alanine 5.0 quality %

1N hydrochloric acid is adjusted to pH7.5

SD Alochol 40 50.0

The residue of purifying waste water

Comparative example 1

SD Alochol 40 50.0 quality %

The residue of purifying waste water

Comparative example 2

Glycerol 5.0 quality %

SD Alochol 40 50.0

The residue of purifying waste water

Comparative example 3

Beta-alanine 5.0 quality %

SD Alochol 40 50.0

The residue of purifying waste water

Comparative example 4

L-lysine one hydrochlorate 5.0 quality %

SD Alochol 40 50.0

The residue of purifying waste water

Comparative example 5

L-lysyl-hydroxyproline 5.0 quality %

1N hydrochloric acid is adjusted to pH7.5

SD Alochol 40 50.0

The residue of purifying waste water

With the water quantities before smearing is the results are shown in the table of water quantities rate of change (%) after 100% o'clock the smearing.

Confirmed the persistence height that wetting agent of the present invention and composition for external application increase the cuticlar water component of skin, moistening effect excellence, preserve moisture.Confirmed that also wetting agent ratio of the present invention is all the time by the glycerol effect excellence of extensively using as wetting agent.And then confirmed that wetting agent of the present invention also likens the L-lysyl-hydroxyproline effect excellence for the present invention similarly with lysine being the dipeptides of constituent to than aminoacid effect excellences such as Beta-alanine, L-lysines.

[table 1] cuticlar water component variation rate (%) result

	Confection	Smeared 2 days	Smeared 4 days
				Embodiment 1	L-lysyl-Beta-alanine	??147.4	??163.4
Comparative example 1	??-	??118.7	??120.7
				Comparative example 2	Glycerol	??114.7	??121.9
Comparative example 3	Beta-alanine	??109.1	??119.0
				Comparative example 4	L-lysine hydrochloride	??119.3	??111.6
Comparative example 5	L-lysyl-hydroxyproline	??109.2	??112.1

[estimation of stability]

For L-lysyl-Beta-alanine one hydrochlorate (embodiment 2), L-lysine (comparative example 6), Beta-alanine (comparative example 7), prepare following composition for external application, and estimate stability.

Astringent quality %

Ethanol 3

Glycerol 2

Medicament 5

1,3 butylene glycol 3

POE (60) hardened castor oil 0.4

Citric acid 0.03

Trisodium citrate 0.07

Sodium versenate 0.02

The residue of purifying waste water

Embodiment 2 L-lysyl-Beta-alanines one hydrochlorate

Comparative example 6 L-lysines

Comparative example 7 Beta-alanines

For embodiment 2, comparative example 6 and comparative example 7, each 50g is put into the 50mL corrugated tubing and covers stopper, in 50 ℃ temperature chamber, preserved 1 month, for cosmetic variation and abnormal smells from the patient, judge according to following benchmark.

(outward appearance)

◎: good cosmetic variation such as (do not have fully variable color, separation, white opacity, crystallization) separating out

Zero: good substantially (change although find part, do not become problem big variation like that)

△: bad substantially (part exists variable color, separation, white opacity, crystallization cosmetic variation such as to separate out)

*: badly (exist variable color, separation, white opacity, crystallization significant cosmetic variation such as to separate out

(abnormal smells from the patient)

◎: good (no change)

Zero: good (almost no change) substantially

△: bad substantially (changing)

*: bad (significant variation is arranged)

[table 2]

As seen from the experiment, the stability of the abnormal smells from the patient of the composition for external application that is combined with L-lysyl-Beta-alanine one hydrochlorate of the present invention and outward appearance is all excellent.In addition, the stability of the abnormal smells from the patient of the composition for external application that is combined with Beta-alanine of comparative example 6, outward appearance is also all excellent.On the other hand, though the excellent in stability of the composition for external application outward appearance that is combined with L-lysine of comparative example 7, the deterioration of abnormal smells from the patient is strong.

Following formulation example as composition for external application of the present invention and wetting agent shows composition for external application.Wherein, any composition for external application all has excellent moistening effect.

Formulation Example 1: emulsifiable paste quality %

Stearic acid 5.0

Octadecanol 4.0

Isopropyl myristate 18.0

Glyceryl monostearate 3.0

Propylene glycol 10.0

L-lysyl-Beta-alanine one hydrochlorate 3.0

Caustic potash 0.2

Sodium sulfite 0.01

Antiseptic is an amount of

Spice is an amount of

The ion exchange water residue

(method for making) adds L-lysyl-Beta-alanine one hydrochlorate, propylene glycol and caustic potash in ion exchange water, the dissolving heating also keeps 70 ℃ (waters).Mix other composition, heating and melting also keeps 70 ℃ (oil phases).Slowly add oil phase at aqueous phase, after all adding is finished, keep this temperature a period of time that reaction is taken place.Use the blender uniformly emulsify then, be cooled to 30 ℃ simultaneously, thereby make well-beaten.

Formulation Example 2: emulsifiable paste quality %

Stearic acid 6.0

Anhydrosorbitol monostearate 2.0

Polyoxyethylene (20 moles) anhydrosorbitol monostearate 1.5

Propylene glycol 10.0

L-lysyl-Beta-alanine dihydrochloride 7.0

Tricaprylin 10.0

Squalene 5.0

Sodium sulfite 0.01

Ethylparaben 0.3

Spice is an amount of

The ion exchange water residue

(method for making) adds L-lysyl-Beta-alanine dihydrochloride, propylene glycol in ion exchange water, the dissolving heating also keeps 70 ℃ (waters).Mix other composition, heating and melting also keeps 70 ℃ (oil phases).Add oil phase at aqueous phase, carry out pre-emulsifying, reuse blender uniformly emulsify is cooled to 30 ℃ simultaneously well-beaten then, thereby makes.

Formulation Example 3: emulsifiable paste quality %

Octadecanol 7.0

Stearic acid 2.0

Hydrogenated lanolin 2.0

Squalane 5.0

2-octyldodecanol 6.0

Polyoxyethylene (25 moles) spermaceti alcohol ether 3.0

Glyceryl monostearate 2.0

Propylene glycol 5.0

DL-lysyl-Beta-alanine one hydrochlorate 0.001

Spice is an amount of

Sodium sulfite 0.03

Ethylparaben 0.3

The ion exchange water residue

(method for making) adds DL-lysyl-Beta-alanine one hydrochlorate, propylene glycol in ion exchange water, the dissolving heating also keeps 70 ℃ (waters).Mix other composition, heating and melting also keeps 70 ℃ (oil phases).Add oil phase at aqueous phase, carry out pre-emulsifying, reuse blender uniformly emulsify is cooled to 30 ℃ simultaneously well-beaten then, thereby makes.

Formulation Example 4: quality of the emulsion %

Stearic acid 2.5

Spermol 1.5

Vaseline 5.0

Liquid paraffin 10.0

Polyoxyethylene (10 moles) monoleate 2.0

Polyethylene glycol 1500 3.0

Triethanolamine 1.0

D-lysyl-Beta-alanine 10.0

Sodium sulfite 0.01

Ethylparaben 0.3

CVP Carbopol ETD2050 0.05

Spice is an amount of

The ion exchange water residue

(method for making) dissolves CVP Carbopol ETD2050 (A phase) in a spot of ion exchange water.Add D-lysyl-Beta-alanine, polyethylene glycol 1500 and triethanolamine in remaining ion exchange water, heating for dissolving also keeps 70 ℃ (waters).Mix other composition, heating and melting also keeps 70 ℃ (oil phases).Add oil phase at aqueous phase, carry out pre-emulsifying, add A again and also use the blender uniformly emulsify mutually, be cooled to 30 ℃ simultaneously well-beaten after the emulsifying, thereby make.

Formulation Example 5: emulsion

(oil phase part) quality %

Octadecanol 1.5

Squalene 2.0

Vaseline 2.5

Take off flavor liquid lanolin 1.5

Radix Oenotherae erythrosepalae oil 2.0

Isopropyl myristate 5.0

Glyceryl monooleate 2.0

Polyoxyethylene (60 moles) hardened castor oil 2.0

Tocopherol acetate 0.05

Ethylparaben 0.2

Butyl p-hydroxybenzoate 0.1

Spice is an amount of

(aqueous portion) quality %

L-lysyl-Beta-alanine potassium salt 1.0

Sodium sulfite 0.01

Glycerol 5.0

Hyaluronate sodium 0.01

CVP Carbopol ETD2050 0.2

Potassium hydroxide 0.2

The residue of purifying waste water

(method for making) is 70 ℃ of dissolving oil phase parts.Dissolve aqueous portion down at 70 ℃, and mix the oil phase part in aqueous portion, the reuse mulser carries out emulsifying, is cooled to 30 ℃ with heat exchanger then, thereby makes.

Formulation Example 6: jelly quality %

95% ethanol 10.0

Dipropylene glycol 15.0

Polyoxyethylene (50 moles) oleyl alcohol ether 2.0

CVP Carbopol ETD2050 1.0

Caustic soda 0.15

L-arginine 0.1

L-lysyl-Beta-alanine one glutamate, Glu 1.0

Methyl parahydroxybenzoate 0.2

Spice is an amount of

The ion exchange water residue

(method for making) be the uniform dissolution CVP Carbopol ETD2050 in ion exchange water, on the other hand, dissolves polyoxyethylene (50 moles) oleyl alcohol ether in 95% ethanol, adds aqueous phase to.Then, add other composition,, thereby make then with in caustic soda, the L-arginine and come thickening.

Formulation Example 7 beautifying liquids

(A phase) quality %

Ethanol (95%) 10.0

Polyoxyethylene (20 moles) octyldodecanol 1.0

Methyl parahydroxybenzoate 0.15

Pantothenylol ether 0.1

(B phase)

Potassium hydroxide 0.1

(C phase)

Glycerol 5.0

Dipropylene glycol 10.0

Sodium sulfite 0.03

L-lysyl-Beta-alanine oxalates 0.05

CVP Carbopol ETD2050 0.2

The residue of purifying waste water

(method for making) with A phase, C uniform dissolution respectively mutually, adds the A phase and carries out solubilising in mutually at C.Then, add B and fill then mutually, thereby make.

Formulation Example 8: facial film (pack)

(A phase) quality %

Dipropylene glycol 5.0

Polyoxyethylene (60 moles) hardened castor oil 5.0

(B phase)

Olive oil 5.0

Tocopherol acetate 0.2

Ethylparaben 0.2

Spice 0.2

(C phase)

L-lysyl-Beta-alanine succinate 1.0

Sodium sulfite 0.03

Polyvinyl alcohol (saponification degree 90, the degree of polymerization 2000) 13.0

Ethanol 7.0

The residue of purifying waste water

(method for making) with A phase, B phase, C uniform dissolution respectively mutually, adds the B phase and carries out solubilising in mutually at A.Then, they are added C fill then mutually, thereby make.

Formulation Example 9: ointment quality %

Polyoxyethylene (30 moles) cetyl ether 2.0

Glyceryl monostearate 10.0

Liquid paraffin 10.0

Vaseline 40.0

Spermol 6.0

Methyl parahydroxybenzoate 0.1

Butyl p-hydroxybenzoate 0.1

Glyceryl monostearate 2.0

L-lysyl-Beta-alanine one taurine one hydrochlorate 5.0

Propylene glycol 10.0

The ion exchange water residue

Spice is an amount of

(method for making) adds propylene glycol in ion exchange water, the dissolving heating also keeps 70 ℃ (waters).With other composition at 70 ℃ of following mixed dissolutions (oil phase).Add oil phase at above-mentioned aqueous phase, use the blender uniformly emulsify, after cooling, fill, thereby make.

Formulation Example 10: emulsifiable paste quality %

Liquid paraffin 8.0

Vaseline 3.0

Dimethyl polysiloxane 2.0

Octadecanol 3.0

Behenyl alcohol 2.0

Glycerol 5.0

Dipropylene glycol 4.0

Trehalose 1.0

Four (2 ethyl hexanoic acid) pentaerythritol ester 4.0

Single isostearic acid polyoxyethylene glyceride 2.0

Monostearate polyoxyethylene glyceride 1.0

Lipophilic glyceryl monostearate 2.0

Citric acid 0.05

Sodium citrate 0.05

Potassium hydroxide 0.015

Oil-soluble Radix Glycyrrhizae extract 0.1

Retinol cetylate (1,000,000 unit) 0.25

L-lysyl-Beta-alanine sulfate 1.0

Tocopherol acetate 0.1

P-Hydroxybenzoate is an amount of

Phenyl phenol is an amount of

Dibenzylatiooluene is an amount of

Sodium versenate 0.05

The 4-tert-butyl group-4 '-methoxy dibenzoyl methylmethane 0.01

P-methoxycinnamic acid 2-Octyl Nitrite 0.1

Beta-carotene 0.01

Polyvinyl alcohol 0.5

Hydroxyethyl-cellulose 0.5

CVP Carbopol ETD2050 0.05

The residue of purifying waste water

Spice is an amount of

Formulation Example 11: emulsifiable paste quality %

Vaseline 2.0

Dimethyl polysiloxane 2.0

Ethanol 5.0

Behenyl alcohol 0.5

Batilol 0.2

Glycerol 7.0

1,3 butylene glycol 5.0

Macrogol 2000 0 0.5

Jojoba oil 3.0

Squalane 2.0

Hydroxy stearic acid plant sterol ester 0.5

Four (2 ethyl hexanoic acid) pentaerythritol ester 1.0

Polyoxyethylene hardened castor oil 1.0

Potassium hydroxide 0.1

Sodium pyrosulfite 0.01

Sodium hexameta phosphate 0.05

Stearyl glycyrrhetinate 0.1

Pantothenylol ether 0.1

Albumin 7.0

Tranexamic acid methyl nitrosourea hydrochlorate 11.0

L-lysyl-Beta-alanine phosphate 1.0

L-lysyl-Beta-alanine aspartate 1.0

Tocopherol acetate 0.1

Hyaluronate sodium 0.05

P-Hydroxybenzoate is an amount of

Sodium versenate 0.05

The 4-tert-butyl group-4 '-methoxy dibenzoyl methylmethane 0.1

Di-p-methoxy cinnamic acid list-2 ethyl hexanoic acid glycerol ester group ester 0.1

Iron oxide yellow is an amount of

Xanthan gum 0.1

CVP Carbopol ETD2050 0.2

The residue of purifying waste water

Formulation Example 12: astringent quality %

1,3 butylene glycol 6.0

Glycerol 4.0

Oleyl alcohol 0.1

POE (20) sorbitan monolaurate 0.5

POE (15) Laurel alcohol ester 0.5

Ethanol 10.0

L-lysyl-Beta-alanine one lactate 0.3

The residue of purifying waste water

Formulation Example 13: astringent quality %

(pure phase)

Ethanol 10.0

Oleyl alcohol 0.1

POE (20) sorbitan monolaurate 0.5

POE (15) lauryl ether 0.5

Antiseptic is an amount of

Spice is an amount of

(water)

L-lysyl-Beta-alanine Radix Betae alkali salt 20.0

1,3 butylene glycol 6.0

Glycerol 4.0

The ion exchange water residue

Formulation Example 14: solid, powdery foundation cream quality %

Talcum 15.0

Sericite 10.0

Spherical nylon powder 10.0

Porous anhydrous silicic acid powder 15.0

Boron nitride 5.0

Titanium dioxide 5.0

Ferrum oxide 3.0

Zinc stearate 5.0

L-lysyl-Beta-alanine toluene fulfonate 1.0

The liquid paraffin residue

Three isooctyl acid glyceride 15.0

Sesquialter oleic acid sorbitan esters 1.5

Antiseptic is an amount of

Spice is an amount of

Formulation Example 15: water-in-oil emulsion foundation cream quality %

Spherical nylon 10.0

Porous anhydrous silicic acid powder 8.0

Mica titanium 2.0

Siloxane treated sericite 2.0

Siloxane treated Muscovitum 12.0

Siloxane treated titanium dioxide 5.0

Siloxane treated ferrum oxide 2.0

The ion exchange water residue

L-lysyl-Beta-alanine 1.0

Decamethyl Pentamethylene. siloxanes 18.0

Dimethyl polysiloxane 5.0

Squalane 1.0

POE modification dimethyl polysiloxane 2.0

Antiseptic is an amount of

Spice is an amount of

Formulation Example 1～15 resulting composition for external application, what all cooperated with embodiment 1 is same, shows the good moisture preserving effect, and excellent in stability, usability excellence.

Claims (2)

1. a wetting agent contains the chemical compound more than a kind or 2 kinds that is selected from lysyl-Beta-alanine shown in the following general formula (1) and the salt thereof,

2. a composition for external application is characterized in that, contains the chemical compound more than a kind or 2 kinds that is selected from above-mentioned lysyl-Beta-alanine chemical compound and the salt thereof.